RhoA/ROCK regulation of neuritogenesis via profilin IIa–mediated control of actin stability

JS Da Silva, M Medina, C Zuliani, A Di Nardo… - The Journal of cell …, 2003 - rupress.org
JS Da Silva, M Medina, C Zuliani, A Di Nardo, W Witke, CG Dotti
The Journal of cell biology, 2003rupress.org
Neuritogenesis, the first step of neuronal differentiation, takes place as nascent neurites bud
from the immediate postmitotic neuronal soma. Little is known about the mechanisms
underlying the dramatic morphological changes that characterize this event. Here, we show
that RhoA activity plays a decisive role during neuritogenesis of cultured hippocampal
neurons by recruiting and activating its specific kinase ROCK, which, in turn, complexes with
profilin IIa. We establish that this previously uncharacterized brain-specific actin-binding …
Neuritogenesis, the first step of neuronal differentiation, takes place as nascent neurites bud from the immediate postmitotic neuronal soma. Little is known about the mechanisms underlying the dramatic morphological changes that characterize this event. Here, we show that RhoA activity plays a decisive role during neuritogenesis of cultured hippocampal neurons by recruiting and activating its specific kinase ROCK, which, in turn, complexes with profilin IIa. We establish that this previously uncharacterized brain-specific actin-binding protein controls neurite sprouting by modifying actin stability, a function regulated by ROCK-mediated phosphorylation. Furthermore, we determine that this novel cascade is switched on or off by physiological stimuli. We propose that RhoA/ROCK/PIIa-mediated regulation of actin stability, shown to be essential for neuritogenesis, may constitute a central mechanism throughout neuronal differentiation.
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